Immunotherapy for pancreatic cancer

Abstract

Pancreatic cancer, a highly lethal cancer, has the lowest 5-year survival rate for several reasons, including its tendency for the late diagnosis, a lack of serologic markers for screening, aggressive local invasion, its early metastatic dissemination, and its resistance to chemotherapy/radiotherapy. Pancreatic cancer evades immunologic elimination by a variety of mechanisms, including induction of an immunosuppressive microenvironment. Cancer-associated fibroblasts interact with inhibitory immune cells, such as tumor-associated macrophages and regulatory T cells, to form an inflammatory shell-like desmoplastic stroma around tumor cells. Immunotherapy has the potential to mobilize the immune system to eliminate cancer cells. Nevertheless, although immunotherapy has shown brilliant results across a wide range of malignancies, only anti-programmed cell death 1 antibodies have been approved for use in patients with pancreatic cancer who test positive for microsatellite instability or mismatch repair deficiency. Some patients treated with immunotherapy who show progression based on conventional response criteria may prove to have a durable response later. Continuation of immune-based treatment beyond disease progression can be chosen if the patient is clinically stable. Immunotherapeutic approaches for pancreatic cancer treatment deserve further exploration, given the plethora of combination trials with other immunotherapeutic agents, targeted therapy, stroma-modulating agents, chemotherapy, and multi-way combination therapies.